The overall objective of the project is to discover the mechanisms that bacteria use for getting attracted or repelled by chemicals (chemotaxis): 1) How are the chemicals sensed? We now know that there are chemoreceptors for this function. 2) How do bacterial flagella work? We now know that they function by rotating, like a propellor, and they can rotate both clockwise and counterclockwise. 3) How is the sensed information transmitted to the flagella to tell them in which direction to rotate, in order to bring the bacterium toward the attractants or away from the repellents? In 1975 we discovered the methylation of a set of membrane proteins, the so-called methyl-accepting chemotaxis proteins (MCPs). These methylatable proteins play a central role in the mechanism of bacterial chemotaxis: they transmit sensory information collected by the chemoreceptors to the flagella, telling the flagella whether to rotate clockwise or counterclockwise and how long they should do this. In cell-free extracts of bacteria, attractants and repellents are still coupled to the methylation and demethylation processes. This enables us to try to discover the mechanism of this coupling. We shall try to fractionate this system so as to learn the nature of the components involved. How do the MCPs control the direction of rotation of the flagella? We shall try to get a sub-cellular system whose flagella still rotate. Then we shall ask what is required for this rotation and for a change in direction of rotation. The signal sent by the MCPs to the flagella now be identified.